title: Neutrophils have a protective role during early stages of Leishmania amazonensis infection in BALB/c mice.
abstract: Neutrophils are involved in the early stages of immune responses to pathogens. Here, we investigated the role of neutrophils during the establishment of Leishmania amazonensis infection in BALB/c and C57BL/6 mice. First, we showed an accumulation of neutrophils between 6 and 24 h post-infection, followed by a reduction in neutrophil numbers after 72 h. Next, we depleted neutrophils prior to infection using RB6-8C5 or 1A8 mAb. Neutrophil depletion led to faster lesion development, increased parasite numbers and higher arginase activity during the first week of infection in BALB/c mice, but not in C57BL/6 mice. Increased susceptibility was accompanied by augmented levels of anti-L. amazonensis IgG and increased production of IL-10 and IL-17. Because IL-10 is a mediator of susceptibility to Leishmania infection, we blocked IL-10 signalling in neutrophil-depleted mice using anti-IL-10R. Interestingly, inhibition of IL-10 signalling abrogated the increase in parasite loads observed in neutrophil-depleted mice, suggesting that parasite proliferation is at least partially mediated by IL-10. Additionally, we tested the effect of IL-17 in inflammatory macrophages and observed that IL-17 increased arginase activity and favoured parasite growth. Taken together, our data indicate that neutrophils control parasite numbers and limit lesion development during the first week of infection in BALB/c mice.
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: L M A
authors.initials: LM
authors.lastname: Sousa
authors.forename: M B H
authors.initials: MB
authors.lastname: Carneiro
authors.forename: M E
authors.initials: ME
authors.lastname: Resende
authors.forename: L S
authors.initials: LS
authors.lastname: Martins
authors.forename: L M
authors.initials: LM
authors.lastname: Dos Santos
authors.forename: L G
authors.initials: LG
authors.lastname: Vaz
authors.forename: P S
authors.initials: PS
authors.lastname: Mello
authors.forename: D M
authors.initials: DM
authors.lastname: Mosser
authors.forename: M A P
authors.initials: MA
authors.lastname: Oliveira
authors.forename: L Q
authors.initials: LQ
authors.lastname: Vieira
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001119:Arginase / Q000378:metabolism; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007700:Kinetics; D007894:Leishmania mexicana / Q000254:growth & development* / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology*; D059208:Parasite Load; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D020381:Interleukin-17; D016753:Interleukin-10; D001119:Arginase
keywords: IL-10; Leishmania amazonensis; immune response; neutrophils